Objectives: The European Network for the Investigation of Gender Incongruence (ENIGI) is a multicenter prospective cohort study. All participants receive a standardized gender affirming treatment protocol including regular follow-up visits. The current study compared the changes in androgens upon starting hormone treatment and during follow-up in transgender women (TW) with or without gonadectomy by investigating serum total (TT), calculated free testosterone (cFT), DHEA, DHEAS, androstenedione and SHBG.
Methods: This prospective cohort study was part of the ENIGI study. Sex steroids were assessed at baseline and at 12 and 24 months of follow-up using immuno-assay (SHBG, DHEAS) and LC-MS/MS (TT, DHEA, androstenedione). FT was calculated. Gender affirming hormones were initiated at baseline: estrogens (oral or transdermal) and anti-androgens (cyproterone acetate 25-50 mg/day). After orchiectomy the anti-androgen therapy was stopped and the estrogens were continued unchanged. Data from 113 TW with ≥ 2 years of follow-up at the Ghent, Belgium site were analyzed prospectively. Subgroup analyses were performed in TW who underwent orchiectomy (group A, n = 59) vs TW who did not (group B, n = 54), at baseline, pre-operatively vs at month 12, and post-operatively vs a month 24.
Results: In group A, serum TT levels decreased from 572.69 ± 11.76 ng/dl to 18.71 ± 11.91 ng/dl (baseline vs. pre-gonadectomy, P < 0.001) and cFT decreased from 11.34 ± 0.35 ng/dl to 0.26 ± 0.35 ng/dl (baseline vs. pre-gonadectomy, P < 0.001). No further effect of gonadectomy on serum TT and cFT levels could be shown, although a trend towards decrease was observed. SHBG increased post-gonadectomy (P < 0.001). Androstenedione, DHEA, DHEAS decreased from baseline to pre-gonadectomy (P < 0001), but remained stable afterwards. Similarly in group B, serum TT, cFT, androstenedione, DHEA and DHEAS decreased between baseline vs. 12 months (P < 0.001), while SHBG increased (P < 0.001); all variables remained stable afterwards. When comparing both groups after 24 months, no group differences in serum TT levels were found. However, SHBG was shown to be higher in group A vs. group B (73.2 ± 39.6 nmol/l vs. 57.2 ± 37.2 nmol/l respectively, P = 0.004), whereas cFT (0.18 ± 0.12 ng/dl vs. 0.26 ± 0.26 ng/dL, P = 0.016), androstenedione (71.0 ± 32.4 ng/dL vs. 85.3 ± 37.2 ng/dL, P = 0.042) and DHEA (4.99 ± 3.61 µg/L vs. 7.34 ± 4.62 µg/L, P = 0.002) were lower.
Conclusion: Serum TT and cFT levels remained unchanged post-orchiectomy compared to before, if low TT was confirmed when on hormonal treatment (including anti-androgens) reflecting patient compliance. At 24 months of follow-up TW who underwent orchiectomy had lower cFT, androstenedione and DHEA and higher SHBG, compared to those with a continued stable dose of anti-androgens.